Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (53)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Suriano, G.
Right arrow Articles by Seruca, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suriano, G.
Right arrow Articles by Seruca, R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2003, Vol. 12, No. 5 575-582
© 2003 Oxford University Press

Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands

Gianpaolo Suriano1,{dagger}, Carla Oliveira1,2,{dagger}, Paulo Ferreira1, José C. Machado1,3, Maria C. Bordin2, Olivier De Wever4, Erik A. Bruyneel4, Nicole Moguilevsky5, Nicola Grehan2, Timothy R. Porter6, Frances M. Richards6, Ralph H. Hruban7, Franco Roviello8, David Huntsman9, Marc Mareel4, Fátima Carneiro1,3, Carlos Caldas2,* and Raquel Seruca1,3,*

1Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200 Porto, Portugal, 2Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Addenbrooke's Hospital, Cambridge CB2 2XZ, UK, 3Faculdade de Medicina, Hospital de S. João, 4200 Porto, Portugal, 4Laboratory of Experimental Cancerology, UZG, B-9000 Ghent, Belgium, 5Service of Applied Genetics, Institute of Biology and Molecular Medicine, B-6041 Gosselies, Belgium, 6Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, The Medical School, Birmingham B15 2TT, UK, 7Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA, 8Istituto Policattedra di Scienze Chirurgiche, Universita degli Studi di Siena, 53100 Siena, Italy and 9Department of Pathology and Laboratory Medicine, University of British Columbia Vancouver, Canada

Received November 19, 2002; Accepted December 20, 2002

E-cadherin is involved in the formation of cell-junctions and the maintenance of epithelial integrity. Direct evidence of E-cadherin mutations triggering tumorigenesis has come from the finding of inactivating germline mutations of the gene (CDH1) in hereditary diffuse gastric cancer (HDGC). We screened a series of 66 young gastric cancer probands for germline CDH1 mutations, and two novel missense alterations together with an intronic variant were identified. We then analysed the functional significance of the two exonic missense variants found here as well as a third germline missense variant that we previously identified in a HGDC family. cDNAs encoding either the wild-type protein or mutant forms of E-cadherin were stably transfected into CHO (Chinese hamster ovary) E-cadherin-negative cells. Transfected cell-lines were characterized in terms of aggregation, motility and invasion. We show that a proportion of apparently sporadic early-onset diffuse gastric carcinomas are associated with germline alterations of the E-cadherin gene. We also demonstrate that a proportion of missense variants are associated with significant functional consequences, suggesting that our cell model can be used as an adjunct in deciding on the potential pathogenic role of identified E-cadherin germline alterations.

* To whom correspondence should be addressed. Tel: +0044 1223 3319 89; Fax: +0044 1223 3317 53; Email: cc234{at}cam.au.uk and Tel: +351 225570764; Fax: +351 225570799; Email: rseruca{at}ipatimup.pt

{dagger} The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
S. S. Pinho, C. A. Reis, J. Paredes, A. M. Magalhaes, A. C. Ferreira, J. Figueiredo, W. Xiaogang, F. Carneiro, F. Gartner, and R. Seruca
The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin
Hum. Mol. Genet., July 15, 2009; 18(14): 2599 - 2608.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Simoes-Correia, J. Figueiredo, C. Oliveira, J. van Hengel, R. Seruca, F. van Roy, and G. Suriano
Endoplasmic reticulum quality control: a new mechanism of E-cadherin regulation and its implication in cancer
Hum. Mol. Genet., November 15, 2008; 17(22): 3566 - 3576.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
F Carneiro, C Oliveira, G Suriano, and R Seruca
Molecular pathology of familial gastric cancer, with an emphasis on hereditary diffuse gastric cancer
J. Clin. Pathol., January 1, 2008; 61(1): 25 - 30.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. R. Mateus, R. Seruca, J. C. Machado, G. Keller, M. J. Oliveira, G. Suriano, and B. Luber
EGFR regulates RhoA-GTP dependent cell motility in E-cadherin mutant cells
Hum. Mol. Genet., July 1, 2007; 16(13): 1639 - 1647.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
P. Kaurah, A. MacMillan, N. Boyd, J. Senz, A. De Luca, N. Chun, G. Suriano, S. Zaor, L. Van Manen, C. Gilpin, et al.
Founder and Recurrent CDH1 Mutations in Families With Hereditary Diffuse Gastric Cancer
JAMA, June 6, 2007; 297(21): 2360 - 2372.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
K. N. Kangelaris and S. B. Gruber
Clinical Implications of Founder and Recurrent CDH1 Mutations in Hereditary Diffuse Gastric Cancer
JAMA, June 6, 2007; 297(21): 2410 - 2411.
[Full Text] [PDF]

Home page
 J. Med. Genet.Home page
J T Bacani, M Soares, R Zwingerman, N di Nicola, J Senz, R Riddell, D G Huntsman, and S Gallinger
CDH1/E-cadherin germline mutations in early-onset gastric cancer
J. Med. Genet., November 1, 2006; 43(11): 867 - 872.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. R.E. Rees, B. A. Onwuegbusi, V. E. Save, D. Alderson, and R. C. Fitzgerald
In vivo and In vitro Evidence for Transforming Growth Factor-{beta}1-Mediated Epithelial to Mesenchymal Transition in Esophageal Adenocarcinoma
Cancer Res., October 1, 2006; 66(19): 9583 - 9590.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. S. Pereira, A. Teixeira, S. Pinho, P. Ferreira, J. Fernandes, C. Oliveira, R. Seruca, G. Suriano, and F. Casares
E-cadherin missense mutations, associated with hereditary diffuse gastric cancer (HDGC) syndrome, display distinct invasive behaviors and genetic interactions with the Wnt and Notch pathways in Drosophila epithelia
Hum. Mol. Genet., May 15, 2006; 15(10): 1704 - 1712.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
T Frebourg, C Oliveira, P Hochain, R Karam, S Manouvrier, C Graziadio, M Vekemans, A Hartmann, S Baert-Desurmont, C Alexandre, et al.
Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer
J. Med. Genet., February 1, 2006; 43(2): 138 - 142.
[Abstract] [Full Text] [PDF]

Home page
 INT J SURG PATHOLHome page
C. Oliveira, R. Seruca, and F. Carneiro
Genetics, Pathology, and Clinics of Familial Gastric Cancer
International Journal of Surgical Pathology, January 1, 2006; 14(1): 21 - 33.
[Abstract] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Suriano, S. Yew, P. Ferreira, J. Senz, P. Kaurah, J. M. Ford, T. A. Longacre, J. A. Norton, N. Chun, S. Young, et al.
Characterization of a Recurrent Germ Line Mutation of the E-Cadherin Gene: Implications for Genetic Testing and Clinical Management
Clin. Cancer Res., August 1, 2005; 11(15): 5401 - 5409.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
O. De Wever, W. Westbroek, A. Verloes, N. Bloemen, M. Bracke, C. Gespach, E. Bruyneel, and M. Mareel
Critical role of N-cadherin in myofibroblast invasion and migration in vitro stimulated by colon-cancer-cell-derived TGF-{beta} or wounding
J. Cell Sci., September 15, 2004; 117(20): 4691 - 4703.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
V. S. Conlin, S. B. Curtis, Y. Zhao, E. D. W. Moore, V. C. Smith, R. M. Meloche, B. B. Finlay, and A. M. J. Buchan
Helicobacter pylori Infection Targets Adherens Junction Regulatory Proteins and Results in Increased Rates of Migration in Human Gastric Epithelial Cells
Infect. Immun., September 1, 2004; 72(9): 5181 - 5192.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
A R Brooks-Wilson, P Kaurah, G Suriano, S Leach, J Senz, N Grehan, Y S N Butterfield, J Jeyes, J Schinas, J Bacani, et al.
Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria
J. Med. Genet., July 1, 2004; 41(7): 508 - 517.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
M T Landi, A M Goldstein, S Tsang, D Munroe, W Modi, M Ter-Minassian, R Steighner, M Dean, N Metheny, B Staats, et al.
Genetic susceptibility in familial melanoma from northeastern Italy
J. Med. Genet., July 1, 2004; 41(7): 557 - 566.
[Full Text] [PDF]

Home page
 GutHome page
R C Fitzgerald and C Caldas
Clinical implications of E-cadherin associated hereditary diffuse gastric cancer
Gut, June 1, 2004; 53(6): 775 - 778.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
G Keller, H Vogelsang, I Becker, S Plaschke, K Ott, G Suriano, A R Mateus, R Seruca, K Biedermann, D Huntsman, et al.
Germline mutations of the E-cadherin(CDH1) and TP53 genes, rather than of RUNX3 and HPP1, contribute to genetic predisposition in German gastric cancer patients
J. Med. Genet., June 1, 2004; 41(6): e89 - e89.
[Full Text] [PDF]

Home page
 Ann OncolHome page
F. Graziano, B. Humar, and P. Guilford
The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice
Ann. Onc., December 1, 2003; 14(12): 1705 - 1713.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Suriano, M. J. Oliveira, D. Huntsman, A. R. Mateus, P. Ferreira, F. Casares, C. Oliveira, F. Carneiro, J. C. Machado, M. Mareel, et al.
E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells
Hum. Mol. Genet., November 15, 2003; 12(22): 3007 - 3016.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.